| 1. |
- Liu, Jimmy Z, et al.
(author)
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
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Journal article (peer-reviewed)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 2. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Wiklund, Camilla, et al.
(author)
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Prolonged constipation and diarrhea in childhood and disordered eating in adolescence
- 2019
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In: Journal of Psychosomatic Research. - : Elsevier. - 0022-3999 .- 1879-1360. ; 126
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Journal article (peer-reviewed)abstract
- Objectives: Gastrointestinal problems are common in all eating disorders; however, the extent to which these problems predate the onset of eating disorders is not clear. We explored longitudinal associations between childhood gastrointestinal problems and adolescent disordered eating, and assessed whether observed associations are potentially causal or due to familial confounding factors. Methods: Data from a population-based Swedish twin sample were used to investigate associations between parent- and self-reported protracted constipation and diarrhea in childhood and adolescence, and later disordered eating, measured by the Eating Disorders Inventory-2 (EDI). Linear regression models were used to investigate the associations. Possible familial confounding was explored by using a within-twin pair analysis. Results: We found that those who reported a history of constipation at age 15 scored 5.55 and 5.04 points higher, respectively, on the EDI total score at age 15 and 18, compared with those without constipation. Those reporting a history of diarrhea at age 15 scored 5.15 points higher, and the group reporting both problems scored 9.52 points higher on the EDI total score at age 15 than those reporting no problems. We observed that the association between constipation and disordered eating was attenuated in the within-twin pair analysis, but remained positive. Conclusions: Gastrointestinal problems in childhood and adolescence are significantly associated with disordered eating. Associations were partly due to familial confounding, but might also be consistent with a causal interpretation. Clinicians should be aware of the increased risk of disordered eating when following children and adolescents who present with gastrointestinal problems.
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